Intravenous Insulin Administration Research Articles

Management of diabetic keto-acidosis in adult patients admitted to intensive care unit: an ESICM-endorsed international survey

BackgroundGuidelines for diabetic ketoacidosis (DKA) management are limited, resulting in varied practices. This study assessed Intensive Care Unit (ICU) admission criteria, fluid resuscitation, insulin therapy, and metabolic management in adult patients with DKA.MethodsAn international survey of ICU clinicians consisted of 39 items that focused on management of DKA and was endorsed by the European Society of the Intensive Care Medicine. An experienced ICU was defined as a unit admitting > 20 patients with DKA per year.ResultsA total of 522 respondents from 57 different countries participated: 295(57%) worked in Europe, 86(16%) in North America, 25(5%) in South America, 52(10%) in Africa, 52(10%) in Asia and 12(2%) in Oceania. Among respondents, 377(72%) worked in teaching hospitals, 355(68%) in medical-surgical ICUs, and 204(39%) in experienced ICUs. The pH value (< 7.20), arterial or venous bicarbonate concentration (< 15 mmol/L), and the need for continuous intravenous insulin (regardless of the dose) were considered criteria for ICU admission by 362(69%), 240(46%) and 264(51%) respondents, respectively. A protocol for fluid resuscitation was available for 290(63%) respondents, 135(29%) administered isotonic saline only, 173(38%) administered balanced solutions only, and 153(33%) administered both. A protocol for insulin therapy was available for 355(77%) respondents. An initial bolus of intravenous insulin was administered by 228(49%) respondents, 221(48%) used an initial continuous intravenous insulin dose of 0.1 UI/kg/h, 42(9%) used an initial predefined fixed dose, 159(35%) based the initial dose on blood glucose and 39(8%) on blood and/or urine ketones. Fluid choice and modalities of intravenous insulin administration did not differ between experienced and non-experienced ICUs. Intravenous insulin administration was more likely to be initiated upon ICU admission (57%vs.45%, p = 0.04) and less likely after initial fluid resuscitation (27%vs.35%, p = 0.04) in experienced ICUs. Arterial or venous pH was monitored by 408(90%) respondents. Arterial blood gases were favored by 236(52%) respondents and venous blood gases were more likely to be performed in experienced ICUs (30%vs.18%,p < 0.01).ConclusionsThe management of patients with DKA remains heterogeneous worldwide. Future randomized trials are needed, especially regarding fluid resuscitation and insulin therapy.Trial registrationNot applicable.

Survey on blood glucose and electrolyte levels in patients with acute myocarditis treated at Bach Mai Hospital

Background and Objectives:Myocarditis is a condition characterized by inflammation of the heart muscle tissue due to various causes, with viruses being a common cause. During the progression of the disease, damage to the heart muscle can lead to acute heart failure, dangerous arrhythmias, cardiogenic shock, or even cardiac arrest, which can result in rapid death. Clinical markers such as chest pain, shortness of breath, and arrhythmias, along with diagnostic tools like electrocardiograms and cardiac ultrasounds, play a crucial role in diagnosing and predicting the disease. In addition to monitoring vital signs, tracking blood glucose and electrolyte levels is an important criterion for nurses in managing patients with acute myocarditis. This aids in making appropriate care and treatment decisions for each specific patient. The study aims to investigate blood glucose and electrolyte levels and their relationship with the severity of heart failure and ventricular arrhythmias in patients with acute myocarditis. Methods:A retrospective review was conducted on the records of 119 patients with acute myocarditis treated at Bach Mai Hospital from 2017 to 2021. Biochemical results were included in a regression model to assess their correlation with the occurrence of adverse clinical outcomes during hospitalization. Results:Among the 119 patients (66.4% male; average age 33.93 ± 15.87 years), significant electrolyte disturbances included severe hyponatremia (6.7%), severe hypokalemia (5.8%), hyperkalemia (8.1%), and blood glucose disorders (31.1%). Severe hyponatremia was found to be predictive of ventricular arrhythmias and in-hospital mortality. Severe hypokalemia was also predictive of ventricular arrhythmias and in-hospital mortality. Hyperkalemia was associated with a higher risk of ventricular arrhythmias. Patients with severe conditions requiring intensive care, such as intravenous feeding or intravenous insulin administration, demonstrated a higher risk of in-hospital mortality. Conclusion:Severe electrolyte disturbances, such as severe hyponatremia, severe hypokalemia, and hyperkalemia, have prognostic significance in patients with acute myocarditis.

A novel pulse-modulated closed-loop artificial pancreas based on intravenous administration of insulin and glucagon

Current attempts to implement and apply automated control systems for the management of glucose homeostasis in individuals with diabetes are partly successful. In most semi and closed loop control systems to mimic the action of a normal pancreas in diabetes patients, insulin is administered subcutaneously. However, the parameters for insulin diffusion and transport time constants are relatively large and have wide individual variations. Therefore, deviation from a normal meal can result in suboptimal euglycemic control. Stable and reliable closed loop feedback control using continuous glucose monitoring under these conditions is difficult and needs regular interventions from the user. This article describes the translation of the endocrine physiology of a normal pancreas to an electronic equivalent. With this translation, the complex effects of a direct intravenous pulsatile method of insulin and glucagon administration can be simulated in accordance with physiological observations in a healthy subject and has been built with standard electronic components. This device is applicable for any individual and under any condition to automatically maintain the desired optimal euglycemic condition. The insulin and glucagon response control is presented in the same physiological pulsatile manner as is observed in healthy individuals.

The significance of precise diabetes diagnosis: a case of euglycemic diabetic ketoacidosis induced by the introduction of empagliflozin with simultaneous reduction of insulin dosage

Euglycemic diabetic ketoacidosis (euDKA) is a rare but severe metabolic complication of diabetes mellitus characterised by elevated anion gap metabolic acidosis despite normal or mildly elevated blood glucose levels. Sodium-glucose cotransporter 2 inhibitors (SGLT2i) have emerged as effective antidiabetic medications, yet their use is associated with an increased risk of euDKA, especially when coupled with insulin dose reduction. We present the case of a 50-year-old male with a 20-year history of diabetes mellitus, initially managed with insulin and metformin, who developed euDKA following the introduction of empagliflozin and sitagliptin alongside a reduction in insulin therapy. Despite normoglycaemia the patient exhibited symptoms of ketoacidosis, including chronic fatigue, polydipsia, and polyuria. Diagnostic workup revealed metabolic acidosis, elevated inflammatory markers, acute kidney injury and ketonuria. Subsequent specialised laboratory tests confirmed type 1 diabetes mellitus (T1DM) with the presence of anti-glutamic acid decarboxylase (anti-GAD) antibodies and the absence of C-peptide secretion. Management involved fluid therapy, intravenous insulin and glucose administration. This case underscores the diagnostic challenges of euDKA and emphasises the importance of differentiating between T1DM and T2DM, as management strategies vary significantly. Patient education on insulin therapy and injection techniques is crucial to prevent complications such as improper insulin delivery and dose reduction, which can precipitate euDKA. In conclusion, clinicians should be vigilant for euDKA in patients on SGLT2 inhibitors, particularly when insulin dose reduction is involved. Comprehensive patient education and accurate differentiation between diabetes types are essential for timely diagnosis and optimal management, thereby reducing the risk of severe complications.

Impact of Peripheral Versus Central Insulin on Cerebrovascular Compliance in Healthy Young Adults

Objective: Vascular compliance is an essential component of cerebral blood flow regulation. Prior work has shown cerebral vasodilation (elicited by hypercapnia) reduces cerebrovascular compliance (Ci); however, this work has yet to be translated to other vasoactive compounds. Insulin has important vasodilatory effects in the peripheral circulation, but less is known about the role of insulin in cerebrovascular control. Herein, we hypothesized both peripheral (intravenous) and central (intranasal) insulin administration would increase indices of cerebral blood flow and reduce Ci in healthy young adults. Methods: Twenty-five healthy young adults (8 female; 26±7 yrs, 25±3 kg/m2) were assigned to two separate protocols (NCT05244694, NCT05153395). Middle cerebral artery blood velocity (MCAv, transcranial Doppler ultrasound) was measured at baseline and under two study conditions: 1) at the end of a 60 min hyperinsulinemic euglycemic infusion, and 2) 60 min following 160 IU of intranasal insulin. Indices of Ci were calculated using a modified Windkessel model applied to blood pressure (finger photoplethysmography) and corresponding MCAv waveforms collected over a 5-min period (10 waveforms) at baseline and during the aforementioned insulin conditions. Results: Blood glucose remained unchanged throughout both protocols (both p&gt;0.05). MCAv was maintained over time under both insulin conditions (protocol 1: 60±13 to 62±17 cm/s, p=0.635; protocol 2: 58±9 to 53±14 cm/s, p=0.146). In contrast, Ci decreased (0.00028±0.00010 to 0.00021±0.00007 cm/s/mmHg, p=0.010) from baseline during peripheral (intravenous) insulin administration. No change in Ci (0.00049±0.00025 to 0.00040±0.00018 cm/s/mmHg, p=0.189) were observed following intranasal insulin administration. Conclusions: Contrary to our hypothesis, there was no effect of peripheral or central insulin administration on resting MCAv in healthy young adults. However, intravenous (but not intranasal) insulin reduced Ci by approximately 25% from baseline values. These findings advance our understanding of cerebrovascular control mechanisms during insulin exposure and provide the opportunity to extend this work to diseased states characterized by insulin resistance, including diabetes. CAFNR Joy of Discovery (JKL, JP). This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Неотложная помощь при экстренных состояниях в диабетологии

Management of medical emergencies in diabetology is an essential area of interest for anesthesiology and intensive care medicine. The main complications of diabetes mellitus (DM) that require intensive treatment and pose a risk of death are hypoglycemia, diabetic ketoacidosis (DKA), and hyperosmolar hyperglycemic state (HHS). This paper provides an analysis of modern scientific publications devoted to clinical manifestations of hypoglycemia, DKA and HHS, and specific aspects of urgent care in these conditions. As demonstrated by data provided here, intensive therapy of these complications of DM is based on stabilization of blood glucose levels, administration of intravenous insulin in DKA and HHS, as well as infusion therapy and correction of electrolyte disturbances. This work discusses the main medications used for treatment of hypoglycemia, DKA and HHS, along with their dosing regimens and routes of administration. Emphasis is made on measures for prevention of cerebral edema, which the main complication associated with these conditions. Knowledge and strict adherence to therapeutic algorithms in medical emergencies in diabetology will help improve clinical outcomes, reduce the risk of complications and bring down death rates.

Ventricular fibrillation in a dog with refractory hyperkalaemia due to uroabdomen following extradural anaesthesia

AbstractA young adult, crossbreed dog was presented to a referral small animal veterinary hospital with uroabdomen causing a severe hyperkalaemia. Stabilisation of the condition consisted of abdominocentesis and intravenous administration of calcium gluconate, insulin, glucose and crystalloids. The patient was then anaesthetised for diagnostic and therapeutic procedures. An epidural was performed with levobupivacaine due to nociception and requirement for exploratory surgery. Marked bradycardia ensued and was treated with anticholinergics and terbutaline, among other repeated efforts to resolve a pharmaceutically resistant hyperkalaemia. However, cardiorespiratory arrest followed, characterised by ventricular fibrillation. Cardiopulmonary resuscitation utilised cardioversion to achieve return of spontaneous circulation within 16 minutes. After return of spontaneous circulation, serum potassium levels only decreased and remained below 7 mmol/L after repeat abdominocentesis, alongside continued medical therapy. Unfortunately, despite successful recovery from general anaesthesia, the patient later developed surgical wound dehiscence and was euthanased as a result.

Diabetic Ketoacidosis in Children and Adolescents; Diagnostic and Therapeutic Pitfalls.

Diabetic ketoacidosis (DKA) represents an acute, severe complication of relative insulin deficiency and a common presentation of Type 1 Diabetes Mellitus (T1DM) primarily and, occasionally, Type 2 Diabetes Mellitus (T2DM) in children and adolescents. It is characterized by the biochemical triad of hyperglycaemia, ketonaemia and/or ketonuria, and acidaemia. Clinical symptoms include dehydration, tachypnoea, gastrointestinal symptoms, and reduced level of consciousness, precipitated by a variably long period of polyuria, polydipsia, and weight loss. The present review aims to summarize potential pitfalls in the diagnosis and management of DKA. A literature review was conducted using the Pubmed/Medline and Scopus databases including articles published from 2000 onwards. Diagnostic challenges include differentiating between T1DM and T2DM, between DKA and hyperosmolar hyperglycaemic state (HHS), and between DKA and alternative diagnoses presenting with overlapping symptoms, such as pneumonia, asthma exacerbation, urinary tract infection, gastroenteritis, acute abdomen, and central nervous system infection. The mainstays of DKA management include careful fluid resuscitation, timely intravenous insulin administration, restoration of shifting electrolyte disorders and addressing underlying precipitating factors. However, evidence suggests that optimal treatment remains a therapeutic challenge. Accurate and rapid diagnosis, prompt intervention, and meticulous monitoring are of major importance to break the vicious cycle of life-threatening events and prevent severe complications during this potentially fatal medical emergency.

高度の尿糖排泄が遷延したSGLT2阻害薬関連正常血糖ケトアシドーシスの1例(A case of SGLT2 inhibitor–associated euglycemic diabetic ketoacidosis with prolonged high urinary glucose excretion)

40歳代の女性，10年来の糖尿病に対して，sodium–glucose cotransporter 2阻害薬（SGLT2i），dipeptidyl peptidase–4阻害薬，メトホルミンを服用していた。前医に交通外傷による上腕骨骨折で入院し，受傷後8日目に全身麻酔下に手術が行われた。術当日はすべての内服が中止された。術後より嘔気，多尿を認め，術後2日目には頻呼吸が出現した。精査加療目的に同日，救命救急センターに転院となった。血液検査にて，乳酸値が正常であるanion gap開大性の代謝性アシドーシスを認めた。血糖値159mg/dL，尿検査で尿糖3+（1,854mg/dL），ケトン体3+であった。SGLT2iの内服歴，尿中ケトン体陽性，代謝性アシドーシスから正常血糖ケトアシドーシス（euglycemic diabetic ketoacidosis: EDKA）と診断した。脱水の補正，インスリン，グルコースの経静脈的投与により，アシドーシスは改善したが，尿中の高度な糖排泄，多尿は持続した。全身状態は改善し，術後4日目に前医に転院となった。500mg/dL以上の尿中への糖排泄は，SGLT2i中止後も10日間以上持続した。SGLT2i中止後も長期にわたり高度の尿糖排泄が遷延する症例では，多尿，脱水に対して適切な水分管理が必要と考えられる。 A woman in her 40s with diabetes mellitus for 10 years was treated with sodium–glucose cotransporter 2 inhibitors (SGLT2i), dipeptidyl peptidase–4 inhibitor and metformin. Surgery to repair a humerus fracture caused by a car accident was performed on day 8 after the accident at her previous hospital. All medications were stopped on the day of surgery. Nausea and polyuria occurred following surgery. Tachypnea appeared on postoperative day (POD) 2, and she was transferred to our hospital for further treatment. Blood gas analysis showed metabolic acidosis with an open anion gap and normal blood glucose level of 159mg/dL. However, urinalysis showed 3+ glucose (urinary glucose level 1,854mg/dL) and 3+ ketones. She was diagnosed as having euglycemic diabetic ketoacidosis associated with SGLT2 inhibitors. Correction of dehydration and intravenous administration of insulin and glucose tended to improve the acidosis, but her urinary glucose excretion and polyuria persisted. The patient was transferred back to her previous hospital on POD4. Urinary glucose excretion above 500mg/dL persisted for more than 10 days after discontinuation of SGLT2i. Urinary glucose excretion may persist for quite some time after discontinuation of SGLT2i and may require appropriate fluid management to prevent polyuria and dehydration. 糖尿病性ケトアシドーシス（diabetic ketoacidosis: DKA）は代謝性アシドーシス，高血糖，および尿中，もしくは血中のケトン体上昇を認める。DKA患者のうち，血糖値が正常であるものを正常血糖ケトアシドーシス（euglycemic diabetic ketoacidosis: EDKA）として1971年に報告された 1。 Sodium–glucose cotransporter 2阻害薬（SGLT2i）は，近年糖尿病だけでなく，慢性心不全，慢性腎臓病にも適応が拡大された。SGLT2iの重大な副作用にEDKAがある 2。EDKAの急性期の経過に関する報告は多数みとめるが，亜急性期の治療経過に関する報告は少ない。 今回我々は，整形外科術後にEDKAを発症し，SGLT2i中止後も10日以上にわたり尿中に500mg/dL以上の糖排泄が持続した症例を経験したので報告する。 本論文に倫理委員会の承諾は必要がない。また本論文は個人情報保護法に基づいて匿名化がなされており，患者またはその家族より論文の出版に関する同意を得ている。 患 者：40歳代の女性 既往歴：高血圧，糖尿病 内服薬：カナグリフロジン（SGLT2i），テネリグリプチン，メトホルミン，ビソプロロール 現病歴：交通外傷により，左上腕骨近位端骨折，左第1趾基節骨骨折を受傷し前医に入院となった。入院時の身長は160cm，体重は80kg，BMIは31.25であった。SGLT2iを含むすべての内服薬を術当日に中止したうえで，左上腕骨骨折に対して観血的骨整復術を施行された。術後より，嘔気を訴えたため，術後悪心嘔吐として補液，制吐剤の投与がなされた。 術後1日目，SGLT2iを含むすべての内服薬を再開し，食事も再開となった。しかし嘔気が強く服薬はできたものの，食事摂取はできなかった。輸液量500mL/日に対して，6,850mL/日の多尿を認めた。 術後2日目には，嘔気の増悪があり，服薬もできなかった。多尿に加え，頻呼吸が出現し，尿定性検査で尿糖3+，ケトン体3+であった。外部機関による，動脈血液ガス分析（室内気）で，pH 7.131，PCO2 16.3mmHg，HCO3− 5.4mmol/L，anion gapは23.6と高値を示し，anion gap開大性の代謝性アシドーシスを認めた。乳酸値が不明であったことから，メトホルミンによる乳酸アシドーシスも鑑別にあがり，精査加療目的に当救命救急センターへ転院となった。頻呼吸が顕著であり，前医にて重炭酸ナトリウム7% 100mLを投与がなされた。 救命救急センター転院時の意識レベルはGlasgow coma scale E3V5M6であった。経皮的酸素飽和度100%（室内気），脈拍106/分，血圧136/78mmHg，体温37.4度，呼吸数25/分と著明な頻呼吸であり，口腔粘膜の乾燥，ケトン臭を認めた。動脈血液ガス分析（室内気）ではpH 7.146，PCO2 13.2mmHg，HCO3− 4.6mmol/L，BE −22.0mmol/L，乳酸9mg/dLであり，anion gapは15と開大しており，乳酸値は正常であった。血糖値は159mg/dLと正常であり，HbA1cは8.5%であった。その他の血液検査所見をTable 1に示す。尿の定性検査では尿糖3+，ケトン体3+，随時尿のグルコース濃度は1,854mg/dLと高値であった。頭部・胸腹部CT検査では感染巣含め，特記すべき異常所見は認めなかった。 乳酸値が正常であることから，メトホルミンによる乳酸アシドーシスは否定的と考えられた。EDKAの診断基準は除外診断 3，もしくは血糖値の上昇に乏しい（血糖値250mg/dL以下），アシドーシス（pH<7.30，HCO3− <18mEq/L），ケトーシス（血中βヒドロキシ酪酸3mmol/L以上，血中アセト酢酸の上昇，尿ケトン陽性でも代用可）の3つを満たすことであると記載されている 2。本症例では他の代謝性アシドーシスの原因となる疾患を指摘しえないこと，血糖値の上昇に乏しく，pH7.146，HCO3− 4.6mmol/Lと著明な代謝性アシドーシス，尿中ケトン陽性であり，ケトーシスを認めたことから，SGLT2iに伴うEDKAと診断した。同日血中ケトン体の測定を行ったところ，アセト酢酸3,397mmol/L，βヒドロキシ酪酸5,961mmol/Lと著明な上昇を認めた。 術後からの水分バランス，体重の推移をFig. 1に示す。術後1日目の水分バランスはマイナス6,350mL，2日目はマイナス2,700mLであり，食事摂取や水分摂取ができていなかったこともあり，救命救急センター転院時の体重は術前と比較して9kg減少していた。 Water balance and change in body weight over time. 救命救急センター入院後（術後2日目），脱水の補正目的に300mL/時間による輸液を開始した。また，救命救急センター入院3時間後より，ヒューマリン1単位/時間，グルコース7.5g/時間の経静脈的投与を開始した。救命救急センター入院13時間後の動脈血液ガス分析（室内気）では，pH 7.277，PCO2 22.3mmHg，HCO3− 10.4mmol/L，BS 172mg/dLとアシドーシスは残存するもanion gapは11.6と正常値を示した。脱水の補正のため，術後2日目には6L/日，3日目には10L/日を超える輸液がなされた（Fig. 1）。 術後4日目の動脈血液ガス分析ではpH 7.481，PCO2 35.7mmHg，HCO3− 26.7mmol/L，BS 150mg/dLとpHも正常化し，血液検査でアセト酢酸967mmol/L，βヒドロキシ酪酸1,894mmol/Lと救命センター入院時と比較して改善を認めたため，同日前医に帰院となった。 帰院後も輸液，ヒューマリンの持続投与と糖質の補充を継続した。救命救急センターでは絶食管理としていたが，前医に帰院した術後4日目から経口摂取が再開され摂取可能であった。その後も，2,000mL/日以上の多尿が持続したことから，輸液は漸減しながらも術後13日目まで継続した。 術後の血糖値，尿糖の推移をFig. 2に示す。術後2日目（カナグリフロジン最終服用から1日後）には尿中の糖排泄は1,854mg/dLであり，術後3日目（カナグリフロジン最終服用から2日後）には尿中の糖排泄は2,477mg/dLと高値を示した。術後8日目（カナグリフロジン最終服用から7日後）でも651mg/dLの糖排泄であった。術後9日目にヒューマリンの持続投与を終了し，術後10日目より，テネグリプチン，メトホルミンを再開した。カナグリフロジン最終服用から11日間にわたり尿糖3+（500mg/dL以上）の尿中への糖排泄がみられた（Fig. 2）。 Changes in the levels of blood and urine glucose over time. 術後17日目に自宅退院となった。前医退院日には入院時と比較して体重は8kg減少していた（Fig. 1）。 SGLT2iは新しい血糖降下作用機序を有する2型糖尿病治療薬として2014年4月17日に本邦で発売され，1型糖尿病，慢性心不全，慢性腎臓病などに適応が拡大し，SGLT2iの処方量は年々増加している 4。SGLT2iの作用機序は，腎臓の近位尿細管にあるナトリウム/グルコール共輸送体に作用し，尿中グルコース排出を促進することで，血糖降下作用を示す。SGLT2iの有害な合併症として，EDKAが知られており，SGLT2iの適応が拡大し使用が増加することで，救急医がEDKAに関わる頻度が増加することが予想される。 SGLT2iによるEDKAの発症には以下の機序が知られている 5。SGLT2iの内服により，尿からのグルコース再吸収が抑制されることで相対的な糖質不足となり，糖代謝から脂質代謝にシフトすることに伴い，血中ケトン体濃度が上昇する。血中のケトン体の増加に加え，尿中グルコース排出の促進に伴う浸透圧利尿による脱水，尿中グルコース排出による血糖降下作用により，EDKAを発症する。SGLT2iに関連したEDKAは嘔吐，脱水，インスリンの中止・減量，インスリン分泌促進薬の中止，手術，感染，絶食・または摂取カロリーの減量，大量飲酒などによって引き起こされる 6。手術によりEDKAを発症する可能性があるため，術前3日前からの休薬が推奨されている 7。本症例ではSGLT2iの休薬が術当日のみになり，術当日の絶食による糖質不足に手術侵襲などが加わりEDKAを発症した可能性が考えられた。 EDKAの症状は一般的なDKAと同様であり，悪心，嘔吐，腹痛が最も多く報告される 2。一方で，血糖値が正常であることから，診断が難しく50%以上の症例で診断が遅れることが報告されている 2。本症例でも，頻呼吸，尿中ケトン体が陽性であったことから前医でもDKAを強く疑ったが，血糖値が159mg/dLであったため確定診断には至らなかった。また，血液ガス分析にてanion gap開大性の代謝性アシドーシスを認めたため，メトホルミンによる乳酸アシドーシスも鑑別に挙がり，前医では十分な評価ができず診断が遅れた。 EDKAの初期治療は通常のDKAと同様に輸液による脱水の補正である。脱水の補正に続いて，0.02～0.05単位/kg/時間でインスリンの持続静脈投与を開始する 2。通常のDKA管理と異なり，低血糖を回避するために，インスリン注入と同時期より，10%のブドウ糖を125mL/時間で開始し 8，血糖値の目標は150～200mg/dLとする 6。その後，カリウムを中心とした電解質補正を行い，重炭酸，アニオンギャップ，pHの正常化をもって治療を終了する。本症例では，低血糖にならないように十分なモニタリングを行ったうえで，インスリンを0.014単位/kg/時間，ブドウ糖を7.5g/時間で投与した。集中治療室で治療された31例のDKA患者の報告 9ではアニオンギャップの正常化に要した時間は中央値で10.4時間とされている。本症例ではアニオンギャップの正常化（12以下）には13時間を要した。本症例では低血糖を懸念したため，文献に記載されているよりも少量のインスリン投与を行ったことで，細胞内への十分な糖質の補充ができず，ケトアシドーシスが遷延した可能性がある。正常血糖ケトアシドーシスにおいても，十分な糖質補充とインスリンの投与が有効であるか，今後の検討が必要である。 カナグリフロジンの代謝動態を調べた研究 10によると，カナグリフロジンを2週間服用した場合，血中薬物濃度の半減期は11.81時間とされている。本症例と同様にカナグリフロジン100mgを服用した場合，おおよその尿中グルコース排泄量はカナグリフロジン服用前と比較して服用当日でプラス100g/日，翌日でプラス60g/日，翌々日でプラス20g/日であった。本症例では，カナグリフロジンの最終服用から2日後の尿中グルコース濃度は2,477mg/dL，尿量は9,240mL/日であったことから，約170g/日の糖が尿中から排泄されたと考えられた。同様に最終服用から3日後は130g/日，7日後で70g/日の尿糖排泄を認めた。また，カナグロフロジン中止後，血糖値は100〜200mg/dLにも関わらず，中止後11日間にわたり尿糖は3+であった。カナグリフロジンの血中薬物濃度が低下して以降も，持続的な薬理学的反応としての尿中グルコース排泄は過去にも報告されている 11, 12。これらの原因として，SGLT2iは内服後，血液中より腎臓に多く分布しており，局所的な薬物濃度が維持されている可能性，代謝酵素の多型，腎機能障害による半減期の延長，薬物の親油性が高く脂肪組織への分布などが挙げられている。本症例では，尿糖排泄が持続した原因として，腎局所でSGLT2iの薬物濃度が維持されている可能性があること，BMI 30以上の肥満であり脂肪組織へSGLT2iが分布していた可能性が考えられた。尿糖陽性である期間は浸透圧利尿により多尿となり，脱水になりやすいことが考えられる。本症例のように，SGLT2i中止後も長期にわたり高度の尿糖排泄が遷延する症例では，多尿，脱水に対して適切な水分管理が必要と考えられる。 整形外科術後にSGLT2iに関連したEDKAの症例を経験した。SGLT2i中止後も長期にわたり高度の尿糖排泄が持続する可能性があり，多尿，脱水に対して適切な水分管理が必要と考えられる。 本論文の投稿にあたり，開示すべき利益相反はない。

PMON80 Case of Cushing's Disease That Presented as Diabetic Ketoacidosis and Successfully Treated With Stereotactic Radiosurgery During the COVID-19 Pandemic

Abstract Background Although Cushing's disease is known to impair glucose metabolism, diabetic ketoacidosis (DKA) as its initial presentation has been reported in only a few case reports. The first-line treatment for Cushing's disease is transsphenoidal surgery, but safety concerns during the COVID-19 pandemic has led to the utilization of other treatment options. We present a case of Cushing's disease that presented initially as DKA and was successfully treated with stereotactic radiosurgery. Case Presentation Our patient was a 36-year-old female known to have diabetes mellitus and hypertriglyceridemia for one year. She presented with one-week history of generalized weakness, blurring of vision, and elevated blood pressure. Her blood glucose level was high at 523 mg/dL, associated with ketosis and metabolic acidosis. She was diagnosed with diabetic ketoacidosis which resolved after hydration and intravenous insulin administration. Further history revealed that she has been experiencing progressive weight gain and infertility for the past five years. She had cushingoid features including obesity, scalp hair thinning, moon facies, acne, hirsutism, and buffalo hump. Midnight salivary cortisol was high at 9.34 ng/mL (0.20-4. 00 ng/mL). Low dose dexamethasone suppression test showed an unsuppressed serum cortisol level at 31.2 mcg/dL (&amp;lt;1.8 mcg/dL). Adrenocorticotropic hormone (ACTH) level was high at 88.5 pg/mL (&amp;lt;46 pg/mL) and pituitary magnetic resonance imaging (MRI) showed an enlarged pituitary gland measuring 13.4 mm in the craniocaudal dimension with leftward displacement of the pituitary stalk. She was diagnosed with Cushing's disease and was initially advised transsphenoidal surgery. Due to concerns of COVID-19 transmission, the team and the patient decided to do stereotactic radiosurgery (SRS). The procedure was performed without complication. At 2 months follow-up, there was noted improvement of blurring of vision, normalization of cortisol level to 20.72 mcg/dL (4.30-22.40 mcg/dL), and a decreased ACTH level at 62.19 pg/mL. There was a 4 mm decrease in the craniocaudal dimension of the pituitary gland on repeat pituitary MRI. Thyroid stimulating hormone (TSH) level normalized from 0.209 to 0.647 uIU/mL (0.55-4.78 uIU/mL), and the glycohemoglobin decreased from 11.5% to 6.3%. Hypertension was controlled on one medication. Conclusion Stereotactic radiosurgery is usually reserved as a secondary option to transsphenoidal surgery. On average, normalization of cortisol levels after SRS takes 14 months. In our patient, the serum cortisol decreased to within normal levels at only 2 months after SRS. While a longer follow-up is desirable in order to assess the durability of control of hypercortisolemia, our case demonstrates that stereotactic radiosurgery is a safe and effective treatment option for Cushing's disease during the COVID-19 pandemic, when safety protocols and decreased hospital and patient resources might hinder the performance of transsphenoidal surgery. Presentation: Monday, June 13, 2022 12:30 p.m. - 2:30 p.m.

Risk factors, prevention and treatment of hypoglycaemia after hyperkalaemia in adult patients using intravenous insulin: An integrative review.

An integrative review was conducted to synthesize published evidence on the prevention and treatment of hypoglycaemia and patient risk factors, in adult patients treated for hyperkalaemia with intravenous insulin and dextrose. This review followed the framework by Whittemore and Knafl. Papers included were limited to English language studies involving participants who were aged 18 years and above and admitted in the inpatient acute care and emergency departments. The literature search was performed using five electronic databases (CINAHL, Embase, PubMed, Proquest and Cochrane). A total of 22 studies were included. Two main themes were derived-patient risk factors and prevention-intervention strategies. Five main patient risk factors were lower pretreatment blood glucose (<7 mmol/L), lower weight, renal insufficiencies, older age and nondiabetic. The four subthemes in the prevention-intervention strategies included (i) methods of administration and dosing of intravenous insulin and dextrose, (ii) frequency of blood glucose monitoring, (iii) education to healthcare professionals and (iv) rescue agents. Standardized computerized order sets and integrated decision tool that can advise appropriate prescription of a higher volume of dextrose or lower insulin dose according to patient risk factors, regular monitoring and reinforced education may prevent and mitigate the risk of hypoglycaemia.

Continuous Intravenous versus Subcutaneous Administration of Insulin for Glycemic Variability in Acute Ischemic Stroke.

BackgroundContinuous intravenous infusion (IV) or subcutaneous injection (SC) of insulin was widely applied to control hyperglycemia after ischemic stroke. However, the impact of different administration modes on glycemic variability was unknown.MethodsConsecutive stroke patients treated with intravenous thrombolysis were screened. Subjects who received insulin treatment were included and entered into the IV or SC group according to the respective administration mode. Blood glucose was closely monitored within the first 72 hours, and the target range of glucose was from 7.7 to 10.0 mmol/L for all patients. The variabilities of glucose, assessed using standard deviation of the mean, variable coefficient and range from the maximum to the minimum value, were compared between the two groups.ResultsA total of 130 patients were enrolled with 66 in the IV groups and 64 in the SC group. Compared with the SC group, the IV group had higher glycemic variability evaluated as either standard deviation (2.7 ± 0.7 mmol/L vs 2.2 ± 0.9 mmol/L, p = 0.002), variable coefficient (0.26 ± 0.06 vs 0.23 ± 0.08, p = 0.011) or range (10.0 ± 3.6 mmol/L vs 8.1 ± 3.1 mmol/L, p = 0.001). Multivariate logistic regression analyses found that continuous intravenous infusion was associated with higher level of the standard deviation (adjusted OR 3.01, 95% CI 1.29–7.28, p = 0.011), variable coefficient (adjusted OR 5.97, 95% CI 2.55–13.96, p < 0.001) and range (adjusted OR 6.08, 95% CI 2.63–14.05, p < 0.001).ConclusionContinuous intravenous infusion of insulin was associated with higher glycemic variability than subcutaneous injection in acute stroke patients receiving thrombolysis.

Treatment of critical aluminum phosphide (rice tablet) poisoning with high-dose insulin: a case report

BackgroundAluminum phosphide (rice tablet) is a highly efficient agent for preserving grains against rodents and insects. It accounts for a large number of poisoning cases. Aluminum phosphide poisoning has a high mortality rate of about 90%, and to date, no antidote is available. It releases phosphine gas after exposure to moisture, and this reaction is catalyzed by the acidity of the stomach. Phosphine is then absorbed throughout the respiratory or gastrointestinal tracts and causes toxicity through inhibition of cytochrome c oxidase and formation of highly reactive free radicals. Treatment of patients with aluminum phosphide poisoning is supportive, including mechanical ventilation and vasopressors. The usage of infusion of glucose-insulin-potassium in rice tablet poisoning has been suggested, after its positive beneficial cardiac inotropic effects in patients with beta-blocker and calcium channel blocker poisoning.Case presentationWe report the case of a 30-year-old Iranian woman with critical aluminum phosphide poisoning, presented with hypotension and other signs of shock and severe metabolic acidosis, successfully treated with high-dose regular insulin and hypertonic dextrose and discharged from hospital in good condition. In contrast to our previous experiences, in which nearly all patients with critical aluminum phosphide poisoning died, this patient was saved with glucose-insulin-potassium.ConclusionAluminum phosphide poisoning has a high mortality rate, and to date, no antidote is available. Administration of high-dose intravenous regular insulin and dextrose is suggested as a potential life-saving treatment for patients with critical aluminum phosphide poisoning.

Hamman's Syndrome Accompanied by Diabetic Ketoacidosis; a Case Report.

Hamman's syndrome is an uncommon clinical entity characterized by an idiopathic spontaneous pneumomediastinum as a result of a sudden increase in intra-alveolar pressure. It can be triggered by repeated vomiting or Kussmaul breathing associated with diabetic ketoacidosis (DKA). Careful attention to this particular condition is needed to avoid under-diagnosis and to provide optimal management. Herein, we report a case of an 18-year-old man complaining of chest discomfort and progressive weight loss, ultimately diagnosed with Hamman's syndrome secondary to DKA. The patient's symptoms disappeared after intravenous fluid and insulin administration, while his pneumomediastinum resolved following conservative treatment. Our report highlights the importance of recognition of the links between pneumomediastinum as a cause of chest pain in patients with DKA.

Subcutaneous regular insulin use for the management of diabetic ketoacidosis in resource limited setting.

The standard recommendation of insulin therapy for patients with DKA is the administration of slow continuous intravenous (IV) regular insulin. Currently subcutaneous insulin is being recommended as an alternative treatment of DKA in mild and moderate cases in resource-limited settings. The purpose of this study was to assess the effectiveness and safety of six-hourly subcutaneous regular insulin use for the treatment of DKA among children with type one diabetes mellitus. A retrospective cohort study was conducted among 224 DKA episodes which occurred in 161 children who were treated at St. Paul's Hospital Millennium Medical College in Addis Ababa, Ethiopia, from November 2015 to November 2020. Majority (68.8%) of the episodes occurred in newly diagnosed cases. The median time for urinary ketones clearance was 24h. DKA severity was found to be the only significant predictor of time to DKA resolution. Only 13 (5.8%) were treated at the pediatric intensive care unit (PICU), and 27 (12.1%) developed complications during management. No death or neurological complications observed. The six-hourly subcutaneous regular insulin use was found to be safe and effective alternative to slow IV insulin infusion for the treatment of DKA in a non PICU setting. As it resulted in minimum morbidity and no mortality, we recommend its use in the treatment of DKA irrespective of its severity. It can also decrease the health care cost and patients' inconvenience.

Blood Sugar Targets in Surgical Intensive Care—Management and Special Considerations in Patients With Diabetes

30-80% of patients being treated in intensive care units in the perioperative period develop hyperglycemia. This stress hyperglycemia is induced and maintained by inflammatory-endocrine and iatrogenic stimuli and generally requires treatment. There is uncertainty regarding the optimal blood glucose targets for patients with diabetes mellitus. This review is based on pertinent publications retrieved by a selective search in PubMed and Google Scholar. Patients in intensive care with pre-existing diabetes do not benefit from blood sugar reduction to the same extent as metabolically healthy individuals, but they, too, are exposed to a clinically relevant risk of hypoglycemia. A therapeutic range from 4.4 to 6.1 mmol/L (79-110 mg/dL) cannot be justified for patients with diabetes mellitus. The primary therapeutic strategy in the perioperative setting should be to strictly avoid hypoglycemia. Neurotoxic effects and the promotion of wound-healing disturbances are among the adverse consequences of hyperglycemia. Meta-analyses have shown that an upper blood sugar limit of 10 mmol/L (180 mg/dL) is associated with better outcomes for diabetic patients than an upper limit of less than this value. The target range of 7.8-10 mmol/L (140-180 mg/dL) proposed by specialty societies for hospitalized patients with diabetes seems to be the best compromise at present for optimizing clinical outcomes while avoiding hypoglycemia. The method of choice for achieving this goal in intensive care medicine is the continuous intravenous administration of insulin, requirng standardized, high-quality monitoring conditions. Optimal blood sugar control for diabetic patients in intensive care meets the dual objectives of avoiding hypoglycemia while keeping the blood glucose concentration under 10 mmol/L (180 mg/dL). Nutrition therapy in accordance with the relevant guidelines is an indispensable pre - requisite.

18F-FDG PET in Myocardial Viability Assessment: A Practical and Time-Efficient Protocol.

We assessed image quality using a practical and time-efficient protocol for intravenous glucose loading and insulin injection before administration of 18F-FDG for PET myocardial viability evaluation in patients with ischemic cardiomyopathy (ICM), with and without type 2 diabetes mellitus. Methods: The metabolic preparation period (MPP) or optimal cardiac 18F-FDG uptake was determined from the time of intravenous infusion of 12.5 or 25 g of 50% dextrose to the time of 18F-FDG injection. Cardiac 18F-FDG image quality was evaluated according to a 5-point scoring system (from 5, excellent, to 1, nondiagnostic) by 2 independent observers. In cases of disagreement, consensus was achieved in a joint reading. Fifteen patients with ICM who underwent oral glucose loading and intravenous insulin administration served as a reference for MPP comparisons. Results: Fifty-nine consecutive patients (age, 63 ± 10 y; 48 men and 11 women) underwent rest 99mTc-tetrofosmin SPECT/CT and 18F-FDG PET/CT for the evaluation of myocardial viability. 18F-FDG image quality was scored as excellent in 42%, very good in 36%, good in 17%, fair in 3%, and nondiagnostic in 2%. When diabetic and nondiabetic patients were compared, the quality scores were excellent in 29% versus 76%, very good in 41% versus 18%, good in 24% versus 6%, fair in 4% versus 0%, and nondiagnostic in 2% versus 0%. The mean (±SD) quality score was 4.12 ± 0.95, and overall it was better in nondiabetic than in diabetic patients (4.71 ± 0.59 vs. 3.88 ± 0.96; P < 0.0001). Notably, the average MPP was significantly less with intravenous glucose loading than with oral glucose loading (51 ± 15 min vs. 132 ± 29 min; P < 0.0001), paralleled by higher insulin doses (6.3 ± 2.2 U vs. 2.0 ± 1.69 U; P < 0.001). Conclusion: Using a practical and time-efficient protocol for intravenous glucose loading and insulin administration before 18F-FDG injection reduces the MPP by 61% as compared with an oral glucose challenge and affords good-to-excellent image quality in 95% of ICM patients.

Comparative anti‐inflammatory effects of insulin and dexamethasone on cardiovascular biomarkers and antioxidants in miniature donkeys subjected to induced carbohydrate overload

SummaryBackgroundInflammatory responses as a result of carbohydrate (CHO) engorgement have been associated with peripheral tissue insulin resistance.ObjectivesThe aim of this study was to comparatively evaluate the anti‐inflammatory effects of intravenous (i.v.) administration of insulin and dexamethasone on clinical parameters, antioxidants and cardiovascular biomarkers in miniature donkeys subjected to induced CHO overload.Study designProspective, experimental study.MethodsEighteen clinically healthy male miniature donkeys with the age of 5 ± 1 years, weight of 105 ± 6 kg, body condition score of 5 (moderate) and height at the withers of 0.9 ± 0.06 m were used for this study. The animals were randomly assigned into three experimental groups (2 treatments and 1 negative control). Oligofructose (OF) at 10 g/kg of bodyweight was administered via nasogastric tube to induce CHO overload. Six hours later, animals in the treatment groups received IV 3 IU/kg bwt of insulin and 2 mg/kg bwt dexamethasone, respectively.ResultsThe results of this study revealed that heart rate (HR), respiratory rate (RR) and rectal temperature (RT), packed cell volume (PCV), white blood cell (WBC), glucose, homocysteine (Hcy) and cardiac troponin I (cTnI) increased, while the values of superoxide dismutase (SOD) and glutathione peroxidase (GPX) decreased in miniature donkeys subjected to CHO engorgement. All variables (except PCV) returned to normal values within 24 h in treatment groups. In treatment groups, HR and RR were significantly lower than the control group after 12 h. There were no significant differences between insulin and dexamethasone in levels of cTnI, Hcy, SOD, GPX, glucose, PCV and WBC after 24 h.Main limitationsRecording of only antioxidants and cardiovascular biomarkers is insufficient to well define the anti‐inflammatory effects of insulin.ConclusionsIt could be suggested that insulin (3 IU/kg bwt) and dexamethasone (2 mg/kg bwt) may be useful during CHO overload in miniature donkeys.

The effects of Zinc-Methionine on glucose metabolism and insulin resistance during late pregnancy in ewes

This study investigated the effects of dietary supplements of Zinc-Methionine (Zn-Met) on the zinc concentration of the blood and indices such as insulin resistance and glucose tolerance in late-pregnancy ewes to provide a practical solution to prevent metabolic diseases associated with energy status. In this research, 18 Makouei pregnant ewes were selected and randomized into 3 experimental groups: Group 1: Basal diet containing 10.3 mg Zn/kgDM and no zinc supplementation = CTR (Control); Group 2: Basal diet supplemented with low-dose zinc equivalent to the pregnancy requirements (30 mg Zn/kgDM) = LZN; Group 3: Basal diet supplemented with high-dose zinc (300 mg Zn/kgDM) = HZN. Blood samples for insulin resistance and glucose tolerance indices were collected according to standard methods. The results of this study indicated that supplementation of high-dose Zn-Met decreased (P < 0.05) blood glucose and tended (P < 0.1) to reduce the beta-hydroxybutyrate (BHB) concentrations. After intravenous injection of glucose and insulin, none of the glucose tolerance and insulin resistance indices were significant among groups (P > 0.05). However, the intravenous glucose tolerance test (IGTT) showed that the area under the curve (AUC) of serum glucose in the HZN group was numerically lower than that of the LZN and CTR groups. Furthermore, the numerically higher clearance rate (CR) of glucose and more negative glucose AUC following intravenous administration of insulin in Zinc-supplemented groups suggested that the ewes had greater insulin response than control group. The results showed a decrease in blood glucose concentration due to higher zinc intake after insulin injection and supported the evidence for improving insulin sensitivity. In addition, our results showed that ewes receiving zinc supplementation experienced a more favorable state of BHB or NEFA values. In conclusion, Zn-Met supplementation was found to have promising effects in improving energy metabolism in late pregnant ewes. However, further studies are needed to understand the mechanisms involved in regulating lipolysis and energy metabolism.

Use of a Flexible Catheter for the Administration of Subcutaneous Insulin in Diabetic Ketoacidosis: A Feasibility Controlled Clinical Trial.

Although intravenous insulin administration is the standard of care in diabetic ketoacidosis (DKA), subcutaneous insulin administration could be a suitable alternative in resource-limited settings, but pain caused by hourly insulin applications are limiting factors for using it, especially in children. We aimed to assess whether the use of a flexible subcutaneous catheter improves comfort in patients with DKA compared with the usual hourly injections' treatment. We also compared the evolution of metabolic variables in patients with DKA using both insulin administration systems. Randomized feasibility controlled open trial, comparing 2 ways (flexible catheter and steel needle) for the initial insulin administration in children with DKA, who were randomly selected to receive subcutaneous insulin by a flexible catheter or using standard needles. The main outcome was pain, assessed hourly and secondary outcome time to achieve ketoacidosis resolution. Twenty subjects were included (10 by group). There were no differences between groups in baseline lab values (glycemia, urea, sodium, bicarbonate and pH). Pain assessment at first insulin administration was significantly lower in the intervention group (4.5 vs 0 points; P = 0.001). Similar differences between both treatment arms were observed in every pain assessment. There were no differences between groups regarding the time elapsed to achieve ketoacidosis resolution. (11.4±4.3 vs 16±8.4; P = 0.12). No adverse events or DKA complications were observed. The use of a flexible catheter reduced the pain associated with subcutaneous insulin administration in nonsevere DKA. The flexible subcutaneous catheter could be a safe alternative for the treatment of uncomplicated DKA in resource-limited settings.